Alkaline earth metal gold keratinates and process of making same



Patented 'A r. 23', 1940 UNITED STATES;

PATENT oF lcE EARTH LIET'AL GOLD KERATIN- ATES AND PROCESS OF MAKINGSAME Adolf Feldt, Berlin-Oharlottenburg, and Adolf Schmitz,Berlin-Friedenau, Germany, assignors to Schering .Aktiengesellschaft, acorporation of Germany No Drawing. Application September 9, 1936, SerialNo. 99,960. In Germany September 13, i

This inventionrelates to a process for the manufacture oftherapeutically valuable gold compounds.

The] gold compounds of keratins' and their degradation products hithertoemployed in therapy constitute the water soluble alkali metal salts ofthese relatively difiicultly soluble car-boxylic acids;

The present invention is based on our discovery that the alkaline earthmetal salts of these gold keratinic acids also possess. outstandingtherapeutic properties. It should also'particularly be mentioned that bythe conversion of the gold keratinic acids in accordance with the presofalcohol or other'organic solvents miscible with 'It is seen-from theabove that also the solutions whichare'obtaind according to'theinvention by the 'action' of the said alkaline earth metal compoundsonthe dissolved gold keratinic acid com? pounds contain the alkalineearth metal salts of the'gold keratinic acids in relatively pure formandthat these Solutions if desired can themselves be employed fortherapeutic purposes'with- 1 out a'separationof the salts beingabsolutely necessary.

Thelgold keratinic-acids and the keratinates to beconverted into thealkaline earth metal salts can be obtained in various ways. Thus; thereare-applicable for this purpose not only the keratinates and keratinicacids obtained by degradation of keratin-containing materials byalkaline oracidhydroly sisin the presence of reducing agents or withsubsequent reduction, as, for ex- 'ample',' the albumose-like keratindegradation products containing sulphhydryl groups obtained'byjacid'fdegradation' in the presence of tin, but

also such as are "obtained by simple acid degradanot without.simultaneous or: subsequent reduction.

Therecan also be employedas starting materials "keratin degradationproducts which are produced "by enzymatic methods from the keratins.

All these degradation, products" are converted 24 Claims. (01. 260-113)in the known manner into the gold keratinic acid which are thentransformed into the alkaline earth metal salts by the present process.

The alkaline earth-gold keratinates, in particular the calcium salts,exhibit the particular advantage that in their therapeutic.applicationthey are free from the disturbing secondary phenomena which the hithertoknown and employed gold preparationsfrequently; exhibit. In additionthey exhibit against pneumococci infection of the mouse excellentefiects which the known gold keratinates do not exhibit to the sameextent. The following examples illustrate the inven-- tion: l p Example1 300g. of hair are heated on the water bath with 1,200 cc f 18%hydrochloric acid until the whole of the keratin has just passed intosolution. The hydrolysateof this reaction mixture is suitablyneutralized with ammonia and filtered from portions which separate. vlinto the clear.

neutral reacting filtrate 150 cc. of pure 15% gold chloride solution areintroduced? in portions,

Wherebyat the conclusion ofthe-introduction a finely divided precipitatecommences to separate.

The reaction liquid is now treated with caustic soda solution toaweakalk'aline reaction. the

solution allowed to stand for several hours and thereupon filtered fromalittle separated gold. By pouring the clear solution into' fivetimes thequantity of alcohol the sodium salt formed of the ,goldkeratinic acid isprecipitated first as a viscous oil. After 24 hours standing the alcoholis decanted, the residue dissolved in water and the solution filtered.The aqueous solution of the gold keratinateis acidified'withacetic acidand treated with 3-4 times thequantity of alcohol, whereby the goldcompoundis separated as free acid. The fine grained precipitate-isallowed to settle and the alcoholic liquid removed. I The residue isagain stirred with alcohol, filtered with suction and Well Washed withalcohol and. then- The product thus obtained is'sus- I pended in waterand shaken with a suspension.

with ether.

of calcium hydroxide until no further solution of the gold compoundtakes place. The alkaline reacting liquid is filtered from undissolved.portions and the filtrate poured into alcohol, The

calcium salt of the gold keratinic acid precipitates as a finelydividedprecipitate. It is filtered with suction andwashed with alcohol andether. It is freed from adhering. difiicultly soluble impurities bytwice reprecipitating it from aqueous solution with alcohol.;-The;*calcium salt is ob=-" tained as an easily water soluble lightyellow colored powder which contains 4.5 to 4.8% Ca and 11.0 to 11.5%Au.

Example 2 In the same manner as in Example 1 from hair, horn or wool,sodium gold keratinate or the free acid of the gold keratin compound isobtained. The suspension of. the""acid water'is' shake-n with asuspension of strontium hydroxide until interaction has taken place.From the clear fil tered solution the strontium salt isprecipi'tated bypouring into alcohol and purified by several reprecipitations. It isobtained as an easily water soluble powder.

In the same manner as in Example 1 from hair, horn or wool, sodium goldkeratinate is obtained which is converted the free acid by precipitationwith acetic'acid with the addition of alcohol. The suspension of thiscompound in water is shaken with a suspension of magnesium oxide wherebythe magnesium salt of the gold keratinic acid passes intosolution. It isisolated after filtration'of the solution by precipitation.

with alcohol. For'purification from 'difiicultly solubleconstituents itidrep'recipitated several of magnesium carbonate.

times from aqueous solution and in this manner the magnesium saltobtained as aneasily soluble light'y'ellow colored substance.

' Example 4 300 g. of horn are heated with 1,200 cc. of 18% hydrochloricacid on the Water bath. After one hour there are added to the hydrolysisliquid 30 g. of tin in portions with good shaking in the course of halfan hour. After this time has elapsed the whole liquid is neutralizedwith ammonia and filtered. Into the still acid clear solution hydrogensulphide is passed to the complete precipitation of the tin sulphide.After the H precipitate has been filtered with suction, into the clearsolution, from which the dissolved hydrogen sulphide has been removed,for example, by means of a stream of indifferent gas such as carbondioxide or by evacuation and which has been i completely neutralizedwith ammonia, cc. of

a 15%ecld chloride solution are introduced. Thareupon caustic soda lyeis added to Weak a1- kaline reaction, the solution allowed to stand forseveral hours and then filtered from any separated gold. By-pouring' theclear. solution into five times the quantity 'of alcohol, the sodiumsalt of the gold keratinic acid'is precipitated'first as a viscous oil.Bydissolving in Water and repeated precipitation with alcohol thesubstance I is'obtained as a fine powder.

300 g. ofhorn are hydrolyzed with hydrochloric acid with simultaneousreduction with tin as in Example-4. The further treatment takes place upto the addition'of the gold chloride solution in the same manner as inExample 4.

The magnesium salt of the gold keratinic is again dissolved in water,filtered from undis- 10 solvedpo'rtions ai'iol'tl'i e pure c'alcium saltof the goldkeratinic acid precipitated by pouring into alcohol- It isobtained as a powder easily soluble in water. y

Example 6 r 15 In the same manner'asin Example 4 a 10% aqueous solutionof the sodium gold keratinate is produced and acidified withhydrochloric acid. The acid solution is practically neutralized byshaking with a suspension o calcium carbonate. After the liquid naspefiltered'fronl solved portions it'is poured into alcoholand calciumsalt. of the gold keratinic acid c in an analogous manner totht" f ample4. "Instead or am a outlier the c'ipitation of the calciumsaltfof thegold kerat acid also methyl "alcohol,"acetone" and the V11 can beemployed.

Of course, many changes and variations inthe reactionco'nditions, etcl,may befade'ibythose skilled in the art" in accordance wi' 1"the'p1 inciples set forthherein and in l nls nnexe'd v .JI' l 1; l.l\

What we claim is: f I 1 j LAnalkaIineearth metal; gold keratinate.

2. A calcium San or gold" kerat" 3. A magnesium" salt of, V

4. Process for the ct'ur earth metalsa'l't's of gold "k tim a ingreacting 'a' 'go'ldkeratim v kaline earthmet'al compound.

5. Process asset forth in claim 4, where soluble alkaline'earthlmeta'lgold" k ti at 6101 tained is precipitated cibleorgariicsolvent.

6. Process as set forth cla' alkaline earth" metal. goldkei 'a iscipitate'd from their adueou so jtiddbsithe dition o falcoh'ol. I 7f.

7. Pro'cess'as set forth in ll ilnwl, wher' M basic compound or calciumi aus m leage witfii Jim.

a solution oft'he'goldkeratinic'acid. .p

9. Process, as; set forth in. claim 5,- W erih'a" basic"'compound ofmagnesiu ca act with a suspension of the 10. Process afs'sjet foithibasic compoundof ma'ghef with a solution'of the gold 11. Process as setforth p the gold compounds obtained he, lysates produced by acidtreatnient (like: are employed as'startingjmaterials.

12. Process as set forth'irli c 4.', wh keratinates obtained by a d, hyp l'ls i duction du n t e dr l sisant the gold compoundsare employed"'as star terials.

An ali earth meta alt l el .0m:

rein the;

pound (if we e ided tdi lheii a keratin containing ma't'eriah e -e ells?a q eeee e eq. -le u...

16. A strontium salt of a gold compound of the reduced hydrolizationproducts of a keratin containing material.

17. Process for the manufacture of alkaline earth metal salts of goldkeratinates, compris ing reacting an alkaline earth metal compound ofthe group consisting of the oxides, hydroxides and carbonates, with thefree carboxylic group-of a gold keratinate.

18. Process for' the manufacture of alkaline earth metal salts of goldkeratinic acids, comprising reacting the reduced degradation product ofa keratin-containing substance with a goldsalt and causing the formedgold keratinic acidtoreact with a basic earth metal compound.

19. Process for the manufacture of alkaline earth metal salts ofgoldkeratinic acids, which comprises subjecting a keratin-containingsubstance to the action of hydrolyzing and reducing agents, causing thereduced product to react with a gold salt and then treating the goldkeratinic acid with a basic compound of an alkaline earth metal.

20. Process for the manufacture of alkaline earth metal salts ofgoldkeratinic acid, comprisingreducing the degradation products of akeratin-containing material, causing the reduced product to react with'agold salt, neutralizing the reaction mixture with an alkali metal base,

and treating the resulting gold complex in acidified condition with abasic, alkaline earth metal compound.

21. Process for the manufacture of alkaline earth metal salts of goldkeratinic acid obtained 8 by the degradationof keratins followed byconversion to'the gold compound, comprising causing such gold compoundin'the free acid condition to react with a basic compound of an alkalineearth metal. I

22. Process for. the manufacture of alkaline earth metal salts of goldkeratinic acid, which comprises degrading a keratin-containingmaterialwith reduction thereof during the degradation, causing thereduced produc't to react with 15 a gold salt, and then treating theresulting gold complex in the free acid condition with a basic. compoundof an alkaline earth metal.

23. Process for the manufacture of alkaline earth metal salts of goldkeratinic acid, which 20 comprises reducing the degradation products ofa keratin-containing material, causing the resulting material to reactwith a, gold salt, and treating the resulting gold complex in the freeacid condition with a basic compound of an alka- 25 line earth metal. i

24. Process as set forth in claim 11, wherein the. keratin degradationproduct obtained by acid hydrolysis in the presence of tin and convertedinto the gold compound is employed as starting 30 material.

ADOLF FELDT. ADOLF SCHMITZ.

CERTIFICATE OF CORRECTION.

Patent No. 2,197,79 April 25, who. ADOLF FELDT, ET AL.

It is hereby certified that error appears in the printed specificationof the above numbered patent requiring correction as follows: Page 2,second column, line 11.9, claim 6, for the word "their" read --its--;line 68, claim 12, for "keratinates" read --keratin degradationproduct"; lines '70 and 71, same claim, for "are employed as startingmaterials." read is employed as starting material.--; page 5, firstcolumn, line 1h, claim 17, 7 for "keratinate read --keratinic acid; andsecond column, line 27, claim 2b., for the claim reference numeral "11"read and that the said Letters Patent shonld be read with thiscorrection therein that the same may conform to the record of the casein the Patent Office.

Signed and sealed this 18th day of February, A. D. l9hl.

. Henry Van Arsdale, (Seal) 7 Acting Commissioner of Patents.

